241 - Arterial Blood Pressure Targets and Outcomes in Persistent Pulmonary Hypertension of Newborn (PPHN): A Cohort Analysis

Publication Number: 4237.241

Marina Santos Oren, University of Texas Southwestern Medical School, Dallas, TX, United States; Satyan Lakshminrusimha, UC Davis, Sacramento, CA, United States; Lorraine Bautista, University of Texas Southwestern Medical School, Dallas, TX, United States; Kikelomo Babata, UTSW, Dallas, TX, United States; Steven Brown, Parkland Health, Dallas, TX, United States; Vishal Kapadia, University of Texas Southwestern Medical School, Dallas, TX, United States; Abhishek Makkar, University of Texas Southwestern Medical School, Dallas, Texas, United States, TX, United States

Background: PPHN presents with hypoxemia secondary to right-to-left shunt with elevated pulmonary vascular resistance relative to systemic vascular resistance. Increasing mean arterial pressure (MAP) to supraphysiological levels may reverse right-to-left shunt and hypoxemia. However, there is no evidence that targeting higher arterial pressures improves outcomes in infants with PPHN and may increase cardiac afterload.

Objective: To determine the relationship between targeting higher MAP and incidence of extracorporeal membrane oxygenation (ECMO) and/or death in infants ≥ 35 weeks with PPHN.

Design/Methods: Retrospective cohort of infants ≥ 35 weeks with clinical diagnosis and echocardiogram evidence of PPHN treated with inhaled nitric oxide in the first week of age in three level 3 hospitals in Dallas, TX from 2016 to 2022. Exclusion criteria were severe cardiopulmonary malformations. Infants were grouped by the minimum target MAP (lower bound of the target range) into Lower MAP Target (≤ 50 mmHg) and Higher MAP Target (>50 mmHg); 50 mmHg corresponds to the 50th percentile at 40 weeks' gestation. Baseline maternal and neonatal characteristics, echocardiographic findings, vasoactive medication use, and clinical outcomes were compared between the two groups. Primary outcome was ECMO cannulation and/or death. Secondary outcomes were ECMO, death, vasoactive inotrope score, and number of vasoactive medications. Categorical data were compared using χ2 or Fisher exact test and median was compared with Mann-Whitney U-test. Multiple logistic regression was done to control for confounders.

Results: 109 infants met inclusion criteria and had MAP target documented. 82 infants (75%) were in the Lower MAP Target and 27 (25%) in the High Target Group. Baseline characteristics and outcomes are listed on Table 1. Higher MAP Target was associated with greater use of epinephrine (70% vs 40%, p=0.01), more than 2 vasoactive medications (44% vs 22%, p=0.049), maximum inotrope score (30 vs 16, p< 0.01), ECMO (33% vs 11%, p=0.01), and ECMO or death (48% vs 20%, p< 0.01). In multivariate analyses, higher MAP target was independently associated with higher odds of ECMO (OR 4.0, 95% CI 1.4, 11.4, p< 0.01] and ECMO/death (OR 3.1, 95% CI 1.1, 10.5, p=0.03]. Admission FiO2 (per 10% increase) was also associated with ECMO/death (OR 1.3, 95% CI 1.0, 1.6, p< 0.01).

Conclusion(s): Targeting a higher mean arterial pressure (>50 mmHg) was associated with ECMO and ECMO/death in infants ≥ 35 weeks with PPHN. Larger studies are needed to determine optimal strategies for vasoactive agents based on physiologic PPHN phenotype instead of a specific MAP target.

Table 1 - Baseline Characteristics, NICU Course, and Outcomes of Infants With PPHN Based on Mean Arterial Blood Pressure (MAP) Targets
*n (%) compared with Chi-square test; Mean compared with T-test; Median compared with Man-Whitney U-test.
† Median (25th, 75th)
‡ Mean ± Standard Deviation
Abbreviation: PPV = Positive Pressure Ventilation; HFNC = High Flow Nasal Cannula; CPAP: Continuous Positive Airway Pressure; IMV = Intermittent Mechanical Ventilation; MAS = Meconium Aspiration Syndrome; HIE = Hypoxic - Ischemic Encephalopathy; RDS = Respiratory Distress Syndrome; RV = Right ventricular; LV = Left ventricular; iNO = inhaled nitric oxide; OI = Oxygen Index

Table 2 - Multivariate Logistic Regression for ECMO, ECMO / Death, and Death in Infants with PPHN
Abbreviations: ECMO = extracorporeal membrane oxygenation

Figure 1 - Predictive Probability of ECMO and ECMO or Death Based on Lower Mean Arterial Pressure Target
Predicted probability of (A) ECMO and (B) ECMO or death from univariate logistic regression models with the lower mean arterial blood pressure (MAP) target as the sole predictor. Bars display the model-estimated probabilities at the specified MAP thresholds (>35, >40, >45, >50, >55, >60 mmHg); no additional covariates were included.